The Benjamin Waterhouse papers, 1797-1829 (inclusive), consist of Waterhouse's (1754-1846) letters to colleagues, including Lyman Spalding (1775-1821), concerning smallpox inoculation and other medical topics. There are also copies of manuscript letters to Harvard Corporation in which Waterhouse defends himself against allegations he was working against the interests of Harvard Medical School.

Benjamin Waterhouse (1754-1846) was the first Hersey Professor of Theory and Practice of Physic at Harvard Medical School. He introduced vaccination against smallpox using cowpox matter in the United States in 1800. He was also a member of the American Academy of Arts and Sciences and was the head physician at the United States Marine Hospital in Charlestown, Massachusetts from 1807 to 1809. Waterhouse was apprenticed to a physician in Newport at age 16. In 1775, Waterhouse traveled to Europe, where under the guidance of his mother's cousin, physician John Fothergill, he enrolled at the University of Edinburgh, studying medicine with professors such as William Cullen, and then at the University of Leyden in the Netherlands, from which he earned an M.D. in 1780. While attending Leyden, Waterhouse stayed in the home of John Adams, then American minister to the Netherlands. After returning to the United States, he became the first professor of medicine at Harvard Medical School (1782) and was one of the three original members of the Harvard Medical School faculty, alongside John Warren (1753-1815) and Aaron Dexter (1750-1829). After reading a book by English physician Edward Jenner on the use of cowpox matter to vaccinate against smallpox, Waterhouse began to study vaccination, reviewing the available published materials and exchanging letters with colleagues in England, including Jenner. Waterhouse obtained a sample of cowpox matter, a thread soaked with cowpox lymph and placed in a sealed glass vial, which he used to vaccinate his son Daniel, on 8 July 1800. Waterhouse subsequently vaccinated three of his other children, Elizabeth, Benjamin, and Mary. The four children were then experimentally inoculated with smallpox at the Brookline smallpox hospital of Dr. William Aspinwall, and they were found to be immune. Waterhouse sought unsuccessfully to establish a universal vaccination program in the United States.